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Biomedical subjects

Min Lu

Publications and source records attributed to Min Lu.

At least 37 records · Page 2Linked to original sources

[Clinical characteristic analysis of the first human case infected by influenza A (H5N1) in Jiangxi Province].

OBJECTIVE: To describe the clinical, laboratory and radiological presentation of a human case infected by influenza A (H5N1), and to understand its management and prognosis. METHODS: The clinical and autopsy data of the first human case infected by influenza A (H5N1) in Jiangxi Province were collected and analyzed. RESULTS: The first case infected by influenza A (H5N1) in Jiangxi Province was confirmed by laboratory findings with reverse transcription-polymerase chain reaction (RT-PCR) and influenza A (H5N1) isolation. The patient had been healthy in the past and exposed to the environment of bird flu before illness. The initial symptoms included high fever with influenza-like symptoms, and then cough and purulent sputum mixed with blood appeared. The clinical situation deteriorated progressively with occurrence of diarrhea and dyspnea. Laboratory abnormalities included decrease of peripheral white blood cells and lymphocytes, urine protein, dramatic increase of enzymes associated with hepatic injury and myocarditis and decrease of serum albumin. Six days later, penicillin-resistant streptococcus pneumoniae was isolated from multiple sputum cultures. With the deterioration of clinical situation, several other bacteria and fungi were found in sputum culture. Pulmonary infiltrates were evident in right middle and lower lobe at day 5 after illness, and rapidly progressed to involve bilateral lungs as acute respiratory distress syndrome (ARDS)-like changes. The patient was treated with antiviral, antibacterial, and antifungal reagents, and corticosteroids and invasive mechanical ventilation were also administered, but without any improvement. The patient died 27 days after the onset of symptoms and an autopsy was performed. Pathologically, the lungs exhibited diffuse alveolar damage. The lymphocytes in the spleen, the lymph nodes and the tonsils were depleted prominently with histiocytic hyperplasia and hemophagocytic phenomena. Edema and degeneration of myocytes in the heart and extensive acute tubular necrosis in the kidney were observed. CONCLUSION: The prognosis was very poor if influenza A (H5N1) infected human cases was developed as ARDS with multiple organ damage or failure.

Adult↗

[A group of synthetic antimicrobial peptides].

Cecropin A1 (CA), first found in the diapause pupa of Hyalophora cecropia, is an alpha-helix antimicrobial peptide. It has suppressive effect on several strains of bacteria but its effect is moderate. Therefore it is imperative to find new peptides of high lethality to pathogenic bacteria. The structure of CA was modified by increasing its alpha-helix number to improve the antimicrobial activity on the basis of previous works that there is a close relationship between the alpha-helix status of peptide and its antimicrobial activity. Fifteen peptides (GK1-GK15) containing the 1st to 8th amino acids (KWKLFKKI) at N terminus of CA linking with a typical alpha-helix structure by GIG hinge were synthesized. Purity (97%) of GK-8 was confirmed by HPLC and molecular weight (2934.0 Da) was measured by mass spectrometry. Minimum inhibitory concentration (MIC, microg/mL) was used to compare their killing efficiency on various bacteria both Grams-positive and Grams-negative. The results showed the killing efficiency of the modified peptides (GK-1, GK-2, GK-8, GK-10) on various bacteria were much more effective than the original and their MICs were only one percent (0.25 microg/ mL) of CA and magainin. It indicates that typical core alpha-helix of the peptides is essential for their lethality to pathogens and some of modified peptides can serve as attractive candidates for antimicrobial drug discovery. The patent number is PCT/ CN 03/00522.

Amino Acid Sequence↗

[The preparation and spectroscopic characteristics of ytterbium silicate glasses].

Yb3+-doped silicate glasses were prepared at high temperature, which had a small non-linear refractive index coefficient n2 (1.62), lower transformation temperature and lower softening temperature (540 degrees C and 585 degrees C, respectively). The absorption spectrum from 850 to 1100 nm showed that the main peak was at 975 nm with two subpeaks near 908 nm and 944 nm, respectively. Emission peak was at 1,010 nm in the fluorescence spectrum with a 65.5 nm fluorescence half-line width. The integrated absorption cross section, stimulated emission cross section and fluorescence time were caculated to be 3.44 X 10(4) pm2, 0.71 pm2 and 1.05 ms, respectively, which satisfy the requirements of laser glasses.

English Abstract↗

[Investigation on spectroscopic properties of Yb3+ -doped laser glasses].

Yb3+ -doped borosilicate glasses were prepared at high tempreture. The absorption spectra and fluorescence spectra were measured at room temperature. The integrated absorption cross section, stimulated emission cross section and fluorescent time were calculated. The results showed that the main peak wavelength was 975.15 nm in absorption spectra with one subpeak near 937.17 nm; emission peak was at 977.15 nm in fluorescence spectra with one subpeak near 997.42 nm; with increasing the sample thickness from 0.5 to 5 mm, luminescence intensity became greater, and the peak shifted to longer wavelength from 995.79 to 999.02 nm. The effective line width of fluorescence increased from 34.64 to 54.50 nm; Fluorescence lifetime decreased from 1.04 to 1.00 ms.

English Abstract↗

A combination of magnetic permeability detection with nanometer-scaled superparamagnetic tracer and its application for one-step detection of human urinary albumin in undiluted urine.

A rapid (6.5 min) and simple one-step magnetic immunoassay (MIA) has been developed for analysis of human urinary albumin in near patient settings. Polyclonal rabbit anti-human albumin was used as a capture antibody and monoclonal mouse anti-human albumin as a detection antibody in a two-site immunometric assay requiring no additional washing procedures. The polyclonal anti-human albumin was conjugated to silica microparticles (solid phase) and the monoclonal antibody to dextran-coated nanoscaled superparamagnetic particles (tracer). Quantification of human albumin in undiluted urine was performed by adding 2 microL urine to a measuring vial containing solid-phase, superparamagnetic tracer and reaction buffer and then inverting the vial by hand for 20 s. The measuring vial was allowed to stand for 6 min prior to detection, in order for the solid-phase sediment to form at the bottom of the vial. Lastly, the measuring vial was placed into a magnetic permeability detector, which measured the enrichment of superparamagnetic tracer in the sediment due to complex formation with human albumin. Total analysis time was 6.5 min. A linear response was obtained for 0-400 mg/L albumin with a detection limit of 5 mg/L. The total coefficient of variation (CV) was 11% calculated from four consecutive runs on a urine sample containing 11.1 mg/L human albumin during 3 consecutive days. Human urinary albumin analysis was performed on 149 patient samples using the MIA technique and the obtained results showed good correlation with the hospital immunoturbidimetric reference method (y = 1.004x + 4.01, R2 = 0.978, N = 149) and a commercially available point of care albumin analysis provided by HemoCue Inc. (y = 0.98x + 5.8, R2 = 0.833, N = 90).

Albumins↗

Sterol regulatory element-binding protein 1 is negatively modulated by PKA phosphorylation.

Sterol regulatory element-binding protein (SREBP)-1a and -1c are key transcription factors that regulate lipid biosynthesis in cells. We identified that Ser338 located at the NH2 terminus of SREBP-1a is a PKA phosphorylation site in vitro and in HepG2 cells. PKA phosphorylation of this site attenuated DNA occupancy, as revealed by chromatin immunoprecipitation assay, and the ensuing transactivation. In contrast, replacing Ser with Ala [SREBP-1a(N)-S338A] increased transactivation. Although it forms heterodimers with the wild-type SREBP-1a(N) or S338A but not a homodimer with itself, SREBP-1a(N)-S338D (replacing Ser with Asp) decreased DNA binding. Ser314 of SREBP-1c, the counterpart of SREBP-1a Ser338, was also phosphorylated by PKA. Accordingly, the adenovirus-mediated expression of SREBP-1c(N)-S314D in HepG2 cells retarded lipogenesis. Our results indicate that the cAMP-PKA pathway, by phosphorylating SREBP-1, may modulate lipid metabolism in liver cell lines.

Amino Acid Sequence↗

The earliest thymic progenitors in adults are restricted to T, NK, and dendritic cell lineage and have a potential to form more diverse TCRbeta chains than fetal progenitors.

T cell progenitors in the adult thymus (AT) are not well characterized. In the present study, we show that the earliest progenitors in the murine AT are, like those in fetal thymus (FT), unable to generate B or myeloid cells, but still retain the ability to generate NK cells and dendritic cells. However, AT progenitors are distinct from those in FT or fetal liver, in that they are able to produce approximately 100 times larger numbers of T cells than progenitors in fetuses. Such a capability to generate a large number of T cells was mainly attributed to their potential to extensively proliferate before the TCRbeta chain gene rearrangement. We propose that the AT is colonized by T/NK/dendritic cell tripotential progenitors with much higher potential to form diversity in TCRbeta chains than FT progenitors.

Animals↗

Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion.

Human immunodeficiency virus type 1 (HIV-1) continues to spread, principally by heterosexual sex, but no vaccine is available. Hence, alternative prevention methods are needed to supplement educational and behavioural-modification programmes. One such approach is a vaginal microbicide: the application of inhibitory compounds before intercourse. Here, we have evaluated the microbicide concept using the rhesus macaque 'high dose' vaginal transmission model with a CCR5-receptor-using simian-human immunodeficiency virus (SHIV-162P3) and three compounds that inhibit different stages of the virus-cell attachment and entry process. These compounds are BMS-378806, a small molecule that binds the viral gp120 glycoprotein and prevents its attachment to the CD4 and CCR5 receptors, CMPD167, a small molecule that binds to CCR5 to inhibit gp120 association, and C52L, a bacterially expressed peptide inhibitor of gp41-mediated fusion. In vitro, all three compounds inhibit infection of T cells and cervical tissue explants, and C52L acts synergistically with CMPD167 or BMS-378806 to inhibit infection of cell lines. In vivo, significant protection was achieved using each compound alone and in combinations. CMPD167 and BMS-378806 were protective even when applied 6 h before challenge.

Administration, Intravaginal↗

Rapid one-step whole blood C-reactive protein magnetic permeability immunoassay with monoclonal antibody conjugated nanoparticles as superparamagnetic labels and enhanced sedimentation.

A rapid (5.5 min) one-step whole blood C-reactive protein (CRP) magnetic permeability immunoassay utilizing monoclonal antibody conjugated dextran iron oxide nanoparticles (70 nm) as superparamagnetic labels and mixed fractions (1:1 ratio of 15-40 and 60 microm) of polyclonal anti-CRP conjugated silica microparticles for enhanced sedimentation is described. In this one-step assay procedure, a whole blood sample (4 microl) is applied to an assay glass vial, containing both antibody conjugates, and mixed for 30 s. The target analyte, CRP, forms a sandwich complex between the conjugated nanoparticles and microparticles, and, subsequently, the complex sediments under normal gravitation within 5 min to the bottom of the vial. The magnetic permeability increase of the sediment due to the presence of the complexed superparamagnetic nanoparticles is determined using an inductance-based transducer. Assayed patient whole blood samples were compared with the Abbott Diagnostics Architect reference method. A strong linear correlation was observed for the CRP concentration range 0-260 mg/l in whole blood (y=1.001x+0.42, R2=0.982, n=50). The CRP assay presented showed a limit of detection of 3 mg/l and a total imprecision (coefficient of variation) of 10.5%. On the basis of our observations, we propose a rapid, one-step, CRP assay for near-patient testing.

Antibodies, Monoclonal↗

Detection of C-reactive protein utilizing magnetic permeability detection based immunoassays.

A new sensing technology platform integrating magnetic permeability detection and a two-site heterogeneous immunoassay in a one-step analysis is described. As a platform model, measurements of C-reactive protein (CRP), a cardiac and inflammation marker, were performed in a rapid (11.5 min) high-sensitivity (hs) procedure with a low detection limit (0.2 mg/L) and accuracy (CV = 11%). The two-site heterogeneous immunoassay was performed in 1.2-mL disposable reagents vials containing solid phase (polyclonal anti-CRP conjugated silica microparticles), labeling agent (monoclonal anti-CRP conjugated superparamagnetic nanoparticles), and reaction buffer. Whole blood (20 muL) was assayed by introducing the sample into a reagent vial using a glass capillary and mixing its contents by hand for 30 s. After a 11-min sedimentation step, the vial was placed into the coil of the magnetic permeability detector, which measured the enrichment of superparamagnetic nanoparticles in the solid-phase sediment. Magnetic permeability detection and quantification is based on the principle that when paramagnetic materials are placed inside a coil, the inductance of the coil is influenced. Screening of CRP on whole blood patient samples showed good correlation with central hospital measurements for hsCRP (y = 1.018x - 0.021, R(2) = 0.980, n = 103) and normal range CRP (y = 1.02x + 2.53, R(2)= 0.991, n = 33) analyses. The mean differences of the two methods according to the Bland and Altman plots were -0.03 +/- 1.12 mg/L for hsCRP analysis and -3.4 +/- 8.64 mg/L for normal range CRP analysis.

C-Reactive Protein↗

Expression of estrogen receptor alpha, retinoic acid receptor alpha and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells.

Human breast cancer cell lines expressing the estrogen receptor alpha (ERalpha), all-trans-retinoic acid (ATRA) receptor alpha (RARalpha) and cellular retinoic acid binding protein II (CRABPII) genes are sensitive to ATRA-mediated growth inhibition. To study the relationship among ERalpha, RARalpha and CRABPII expression, the protein levels of each member were compared in five breast cancer cell lines (T47D, MCF-7, ZR-75-1, Hs587 T and MDA-MB-231 cells) and two immortalized nontumorigenic breast epithelial cell lines (MTSV1.7 and MCF-10A). ERalpha, RARalpha and CRABPII proteins were detected in T47D, MCF-7 and ZR-75-1 cells but not in other tested cell lines. RARalpha and CRABPII proteins were either reduced or undetectable in T47D/C4:2W and MCF-7/ADR cells with lost expression of ERalpha. Estradiol increased and anti-estrogens (tamoxifen and ICI 164,384) downregulated the expression of both RARalpha and CRABPII proteins in T47D and MCF-7 cells. RARalpha antagonist Ro-41-5253 inhibited CRABPII expression, but not RARalpha expression in estradiol-treated T47D and MCF-7 cells. Suppression of ERalpha by small interfering RNA (siRNA) reduced RARalpha and CRABPII gene expression and siRNA suppression of RARalpha reduced CRABPII expression while having no effect on ERalpha in T47D cells. Transient transfection of either RARalpha or ERalpha expression vectors increased CRABPII expression in MDA-MB-231 cells but only RARalpha, not ERalpha, activated hCRABPII promoter reporter. These results indicate that there is a gene activation pathway in which ERalpha drives RARalpha transcription and RARalpha drives CRABPII transcription in ERalpha-positive human breast cancer cells.

Animals↗

Integrin alpha8beta1-fibronectin interactions promote cell survival via PI3 kinase pathway.

Integrin signaling plays a critical role in many aspects of normal growth, differentiation, and injury response. In the adult, alpha8beta1 is expressed in alveolar myofibroblasts and is upregulated in pulmonary fibrosis and other models of organ injury. Following injury, survival of fibronectin-producing myofibroblasts cells is an important determinant of development of fibrosis. Using stable alpha8-transfected cell lines, we show that interactions of alpha8beta1 with its ligand, fibronectin, promote cell survival during serum deprivation. Multiple cell signaling pathways were activated following fibronectin adhesion, including PI3 kinase and MAP kinase. However, the alpha8-mediated cell survival was blocked by LY294002, a PI3 kinase inhibitor, but not by staurosporine, a PKC inhibitor, or PD98059, a MAPK kinase inhibitor. A dominant negative construct of PI3 kinase also inhibited alpha8-mediated cell survival. Therefore, alpha8-mediated survival appears to be mediated by the PI3 kinase pathway. Survival of alpha8-expressing myofibroblasts may contribute to persistent fibrosis following injury.

Animals↗

Synthesis and anticancer activity of 2-alkylaminomethyl-5-diaryl-methylenecyclopentanone hydrochlorides and related compounds.

Eleven new diaryl-methylenecyclopentanone Mannich hydrochlorides and related compounds were synthesized with different modification on Mannich base and alpha,beta-unsaturated bonds. The glutathione-binding ability, glutathione-s-transferase pi (GSTpi) inhibition and antitumor effect of these compounds were compared. Compounds containing both Mannich base and alpha-unsaturated bond have GSH binding ability, GSTpi inhibitory activity and antitumor effect. Compounds without Mannich base or having a alpha-saturated bond lose GSH binding ability and the antitumor effect. Converting of Mannich base from dimethylaminomethyl group to morpholino, pyrrolidino, or piperidino-methyl groups do not evidently change the antitumor effect. However replacement of phenyl group with methylphenyl group on beta-chain significantly increases cytotoxic effect in breast cancer cells but not in immortalized mammary epithelial cells. Our data suggest that diaryl-methylenecyclopentanones represent a new category of compounds which might inhibit tumor growth through binding to glutathione or thiol proteins.

Antineoplastic Agents↗

Endovenous laser treatment combined with a surgical strategy for treatment of venous insufficiency in lower extremity: a report of 208 cases.

BACKGROUND: We assessed the safety and efficacy of endovenous laser treatment (EVLT) of the saphenous vein combined with a surgical strategy for treatment of deep venous insufficiency in the lower extremity. METHODS: Two hundred thirty venous insufficiencies of the lower limbs in 208 consecutive patients (93 men and 115 women; mean age, 54.15 years) were treated with EVLT combined with surgical strategies. All patients were symptomatic. There were 84 limbs (36.5%) in C(2), 25 (10.9%) in C(3), 109 (47.7%) in C(4), 1 (0.4%) in C(5), and 9 (3.9%) in C(6) (CEAP), and Klippel-Trenaunay syndrome was present in 2 limbs. A total of 119 (51.7%) had perforator vein incompetence. Four therapeutic methods were included in this series according to symptoms, CEAP classification, and venous reflux. Simple EVLT was performed for 15 patients with only great saphenous vein (GSV) incompetence or Klippel-Trenaunay syndrome in 19 lower limbs. EVLT combined with high ligation of the GSV and open ligation of perforators was performed for 5 patients with GSV and perforator incompetence in 5 lower limbs. EVLT was combined with high ligation of the GSV for 76 patients with GSV incompetence in 94 lower limbs. EVLT was combined with external banding of the first femoral venous valve and high ligation of the GSV for 112 patients with primary deep venous insufficiency in 112 lower limbs. All patients were followed up on an outpatient basis for physical examinations and postoperative complaints, and duplex ultrasonography was performed 2 weeks, 6 months, and 1 year after operation. RESULTS: All patients tolerated the procedure well and returned to normal daily activities immediately, achieving a 100% immediate clinical success rate. Spot skin burn injuries occurred in 2 patients (1.0%). Paresthesia in the gaiter area was noted in 15 patients (7.2%). No postprocedural symptomatic deep venous thrombosis or pulmonary embolism occurred. Three patients had local recurrent varicose veins in the calf (1.4%) during a 2- to 27-month follow-up (mean, 6.12 months). Postoperative clinical classes were significantly improved between 2 weeks and 24 months (P = .0001 at 2 weeks and 3 to 18 months; P = .0055 at 24 months compared with before operation), especially in preoperative C(2) to C(3) stage patients, who achieved complete amelioration. CONCLUSIONS: EVLT is a novel minimally invasive treatment with advantages of safety, effectiveness, and simplicity, and it leaves no scars. Its indications can be expanded by combining EVLT with surgical strategies.

Adolescent↗

Severe acute respiratory syndrome associated coronavirus is detected in intestinal tissues of fatal cases.

OBJECTIVES: A significant percentage of confirmed severe acute respiratory syndrome (SARS) patients experienced gastrointestinal symptoms, and the viral sequence was detectable in the stool of most patients. At present, the knowledge of the pathology of the digestive system in SARS patients is limited. Because a resurgence of the SARS epidemic is constantly possible, there is an urgent need to understand the involvement of the digestive system in this new disease. METHODS: We performed seven SARS autopsies in which samples of alimentary tract and digestive glands were examined with routine pathology, electron microscopy (EM), in situ hybridization (ISH), immunohistochemistry, and real-time polymerase chain reaction (PCR). RESULTS: The main histopathological finding was atrophy of the mucosal lymphoid tissue. A few mucosal epithelial cells and lymphocytes in the intestine were positively stained for coronavirus with ISH. SARS-coronavirus (CoV)-like particles were found in the mucosal epithelial cells under EM and mild focal inflammation was detected in the alimentary tract. One patient who experienced severe diarrhea had pseudomembranous enteritis of the ileum. Fatty degeneration and central lobular necrosis were observed in the liver. No evidence of direct viral infection was found in the esophagus, the stomach, the salivary gland, the liver, or the pancreas. CONCLUSIONS: In addition to the lungs, the gastrointestinal tract is another target of SARS-CoV infection, as the intestinal epithelial cells and mucosal lymphoid tissue are infected. The findings provide possible explanations for the gastrointestinal symptoms and the presence of virus in the stool of SARS patients.

Adult↗

The cytoplasmic tail slows the folding of human immunodeficiency virus type 1 Env from a late prebundle configuration into the six-helix bundle.

Effects of the cytoplasmic tail (CT) of human immunodeficiency virus type 1 Env on the process of membrane fusion were investigated. Full-length Env (wild type [WT]) and Env with its CT truncated (DeltaCT) were expressed on cell surfaces, these cells were fused to target cells, and the inhibition of fusion by peptides that prevent Env from folding into a six-helix bundle conformation was measured. For both X4-tropic and R5-tropic Env proteins, DeltaCT induced faster fusion kinetics than did the WT, and peptides were less effective at inhibiting DeltaCT-induced fusion. We tested the hypothesis that the inhibitory peptides were less effective at inhibiting DeltaCT-induced fusion because DeltaCT folds more quickly into a six-helix bundle. Early and late intermediates of WT- and DeltaCT-induced fusion were captured, and the ability of peptides to block fusion when added at the intermediate stages was quantified. When added at the early intermediate, the peptides were still less effective at inhibiting DeltaCT-induced fusion but they were equally effective at preventing WT- and DeltaCT-induced fusion when added at the late intermediate. We conclude that for both X4-tropic and R5-tropic Env proteins, the CT facilitates conformational changes that allow the trimeric coiled coil of prebundles to become optimally exposed. But once Env does favorably expose its coiled coil to inhibitory peptides, the CT hinders subsequent folding into a six-helix bundle. Because of this facilitation of maximal exposure and hindrance of bundle formation, the coiled coil is optimally exposed for a longer time for WT than for DeltaCT. This accounts for the greater peptide inhibition of WT-induced fusion.

CD4 Antigens↗